Higher Tumor/Organ Accumulation Ratio of Porous Dual Infinite Coordination Polymer Nanocomposites for Efficient Tumor Photothermal‐Starvation‐Dual Hypoxia Chemo Synergistic Therapy

Abstract To enhance tumor comprehensive therapeutic effect of nanomedicines, an efficient strategy that integrates polydopamine and IR780 photothermal therapy, glucose oxidase (GOx) starvation therapy, Banoxantrone (AQ4N) and Tirapazamine (TPZ) dual hypoxia chemotherapy is developed in chronological order. Higher tumor accumulation of porous dual infinite coordination polymer nanocomposites are designed and prepared to implement this strategy, in which fluorescent dye IR780 doped hypoxic prodrugs AQ4N and TPZ coordinated with Cu(II) as the core, this core is encapsulated by GOx‐loaded porous polydopamine coordinated with Fe(III) (Fe‐MPDA). These nanocomposites exhibit a particle dimension of 118.5 ± 21.7 nm with pore size of 20.1 nm (pore volume 0.012 cm³ g⁻¹ nm⁻¹), facilitating easy accumulation in tumor tissues. Particularly, their ratio of the area under the curve (AUC) of the tumor/organ drug concentration versus time (AUC_tumor/AUC_organs) is 1.28. Upon reaching the tumor, the nanocomposites release GOx and Fe‐MPDA in initial stage to execute photothermal and starvation therapy, simultaneously enhance the hypoxic level at the tumor site. Then AQ4N and TPZ undergo synergistic chemotherapy in the enhanced hypoxic environment. Animal experiments show a tumor inhibition rate of 100% and a tumor recurrence rate of 0% after 60 d, demonstrating their great potential application for tumor treatment.